Variation in gene expression of presenilins-associated rhomboid-like protein and mitochondrial function in skeletal muscle of insulin-resistant rats.

Multiple factors promote insulin resistance. In this study, we evaluated the mRNA levels of presenilins-associated rhomboid-like protein (PARL) and mitochondrial content and enzyme activity from skeletal muscle isolated from insulin-resistant rats. Rats fed a high-fat diet for 35 days developed moderate insulin resistance, which was determined by an increase in plasma glucose and insulin concentrations following an oral glucose tolerance test. The PARL mRNA level was lower in the insulin-resistant rats than in control animals, and is associated with low mitochondrial content and reduced mitochondrial enzyme activity in the skeletal muscle from the insulin-resistant rats. The results suggest that high-fat-diet-induced insulin resistance is associated with mitochondrial dysfunction in skeletal muscle, and may be the result of the decreased expression of the PARL gene, which encodes the protein with functional significance in mitochondria.